Influence of interferon on adriamycin uptake of cultured tumor cells

Effect of human interferon beta (IFN beta) or interferon gamma (IFN gamma) on cellular uptake of adriamycin (ADM) was measured in 3 in vitro-cultured human tumor cell lines. Pre-incubation of tumor cells with 100 IU/ml of IFN beta or gamma for 6 hr resulted in an increased intracellular ADM concentration, but ADM efflux was not affected by the IFNs. The increase in cellular uptake of ADM was in agreement with both DNA and protein synthesis inhibition. 3H thymidine (3H-TdR) incorporation was remarkably inhibited by ADM with pre-treatment of 100 IU/ml of each IFN, and an additive effect of ADM and IFN on cell growth inhibition could be observed. Similar additive inhibition against tumor-cell proliferation in nude mice, which received combined treatment (twice/week) of IFN gamma (5,000 IU/mouse) and ADM (5-20 micrograms/mouse), was also observed. These results indicate that IFN increases cellular influx of ADM, and antiproliferative activity against tumor cells is enhanced by a combination of IFN and ADM.